Aortic Coarctation: Recent Developments in Experimental and Computational Methods to Assess Treatments for this Simple Condition

Coarctation of the aorta (CoA) is often considered a relatively simple disease, but long-term outcomes suggest otherwise as life expectancies are decades less than in the average population and substantial morbidity often exists. What follows is an expanded version of collective work conducted by the authors\u27 and numerous collaborators that was presented at the 1st International Conference on Computational Simulation in Congenital Heart Disease pertaining to recent advances for CoA. The work begins by focusing on what is known about blood flow, pressure and indices of wall shear stress (WSS) in patients with normal vascular anatomy from both clinical imaging and the use of computational fluid dynamics (CFD) techniques. Hemodynamic alterations observed in CFD studies from untreated CoA patients and those undergoing surgical or interventional treatment are subsequently discussed. The impact of surgical approach, stent design and valve morphology are also presented for these patient populations. Finally, recent work from a representative experimental animal model of CoA that may offer insight into proposed mechanisms of long-term morbidity in CoA is presented

Computational simulations demonstrate altered wall shear stress in aortic coarctation patients previously treated by resection with end-to-end anastomosis

Background.  Atherosclerotic plaque in the descending thoracic aorta (dAo) is related to altered wall shear stress (WSS) for normal patients. Resection with end-to-end anastomosis (RWEA) is the gold standard for coarctation of the aorta (CoA) repair, but may lead to altered WSS indices that contribute to morbidity. Methods.  Computational fluid dynamics (CFD) models were created from imaging and blood pressure data for control subjects and age- and gender-matched CoA patients treated by RWEA (four males, two females, 15 ± 8 years). CFD analysis incorporated downstream vascular resistance and compliance to generate blood flow velocity, time-averaged WSS (TAWSS), and oscillatory shear index (OSI) results. These indices were quantified longitudinally and circumferentially in the dAo, and several visualization methods were used to highlight regions of potential hemodynamic susceptibility. Results.  The total dAo area exposed to subnormal TAWSS and OSI was similar between groups, but several statistically significant local differences were revealed. Control subjects experienced left-handed rotating patterns of TAWSS and OSI down the dAo. TAWSS was elevated in CoA patients near the site of residual narrowings and OSI was elevated distally, particularly along the left dAo wall. Differences in WSS indices between groups were negligible more than 5 dAo diameters distal to the aortic arch. Conclusions.  Localized differences in WSS indices within the dAo of CoA patients treated by RWEA suggest that plaque may form in unique locations influenced by the surgical repair. These regions can be visualized in familiar and intuitive ways allowing clinicians to track their contribution to morbidity in longitudinal studies

Fluid-structure interaction simulation of pulse propagation in arteries : numerical pitfalls and hemodynamic impact of a local stiffening

When simulating the propagation of a pressure pulse in arteries, the discretization parameters (i.e. the time step size and the grid size) need to be chosen carefully in order to avoid a decrease in amplitude of the traveling wave due to numerical dissipation. In this paper the effect of numerical dissipation is examined using a numerical fluid-structure interaction (FSI) model of the pulse propagation in an artery. More insight in the influence of the temporal and spatial resolution of the wave on the results of these simulations is gained using an analytical study in which the scalar linear one-dimensional transport equation is considered. Although this model does not take into account the full complexity of the problem under consideration, the results can be used as a guidance for the selection of the numerical parameters. Furthermore, this analysis illustrates the difference in accuracy that can be obtained using a second-order implicit time integration scheme instead of a first-order scheme. The results from the analytical and numerical studies are subsequently used to determine the settings necessary to obtain a grid and time step converged simulation of the wave propagation and reflection in a simplified model of an aorta with repaired aortic coarctation. This FSI model allows to study the hemodynamic impact of a stiff segment and demonstrates that the presence of a stiff segment has an important impact on a short pressure pulse, but has almost no influence on a physiological pressure pulse. This phenomenon is explained by analyzing the reflections induced by the stiff segment

Elimination of Transcoarctation Pressure Gradients Has No Impact on Left Ventricular Function or Aortic Shear Stress After Intervention in Patients With Mild Coarctation

Objectives: This study sought to investigate the impact of transcatheter intervention on left ventricular function and aortic hemodynamics in patients with mild coarctation of the aorta (COA). Background: The optimal method and timing of transcatheter intervention for COA remains unclear, especially when the severity of COA is mild (peak-to-peak transcoarctation pressure gradient  < 20 mm Hg). Debate rages regarding the risk/benefit ratio of intervention versus long-term effects of persistent minimal gradient in this heterogeneous population with differing blood pressures, ventricular function, and peripheral perfusion. Methods: We developed a unique computational fluid dynamics and lumped parameter modeling framework based on patient-specific hemodynamic input parameters and validated it against patient-specific clinical outcomes (before and after intervention). We used clinically measured hemodynamic metrics and imaging of the aorta and the left ventricle in 34 patients with mild COA to make these correlations. Results: Despite dramatic reduction in the transcoarctation pressure gradient (catheter and Doppler echocardiography pressure gradients reduced by 75% and 47.3%, respectively), there was only modest effect on aortic flow and no significant impact on aortic shear stress (the maximum time-averaged wall shear stress in descending aorta was reduced 5.1%). In no patient did transcatheter intervention improve left ventricular function (e.g., stroke work and normalized stroke work were reduced by only 4.48% and 3.9%, respectively). Conclusions: Transcatheter intervention that successfully relieves mild COA pressure gradients does not translate to decreased myocardial strain. The effects of the intervention were determined to the greatest degree by ventricular–vascular coupling hemodynamics and provide a novel valuable mechanism to evaluate patients with COA that may influence clinical practice. Key Words: aortic hemodynamics, left ventricle function, mild coarctation, peak-to-peak pressure gradient, transcatheter interventionNational Institute of Mental Health (U.S.) (R01 GM 49039)American Heart Association (Postdoctoral Fellowship 16POST26420039

Quantifying the Impact of Altered Hemodynamics and Vascular Biomechanics to Changes in Structure and Function in Native and Corrected Aortic Coarctation

Coarctation of the aorta (CoA) is associated with substantial cardiovascular morbidities despite successful treatment through surgical or catheter-based intervention. Although specific mechanisms leading to these morbidities remain elusive, abnormal hemodynamics and vascular biomechanics are implicated. We used a novel animal model that facilitates quantification of CoA-induced hemodynamic and vascular biomechanics alterations and their impact on vascular structure and function, independent of genetic or confounding factors. Rabbits underwent thoracic CoA at 10 weeks of age (~9 human years) to induce a 20 mmHg blood pressure (BP) gradient using permanent or dissolvable suture thereby replicating untreated and corrected CoA. Computational fluid dynamics (CFD) was performed using subject-specific imaging and BP data at 32 weeks to quantify velocity, strain, and wall shear stress (WSS). Vascular structure and function were evaluated at proximal and distal locations by histology, immunohistochemistry, and myograph analysis. Results revealed proximal systolic and mean BP was elevated in CoA compared to corrected and control rabbits leading to vascular remodeling, endothelial dysfunction proximally and distally, and increased stiffness and reduced active force response proximally. Corrected rabbits had reduced but significant medial thickening, endothelial dysfunction, and stiffening limited to the proximal region despite 12 weeks of alleviated systolic and mean BP (~4 human years) after the suture dissolved. Proximal arteries of CoA and corrected groups demonstrated increased non-muscle myosin expression and decreased myosin heavy chain expression, and this dedifferentiation may influence vascular remodeling and aortic stiffening. CFD analysis of untreated CoA rabbits demonstrated significantly reduced WSS proximal to CoA and markedly elevated WSS distally due to the presence of a stenotic velocity jet. Results from corrected rabbits indicate the velocity jet may have persistent effects on hemodynamics, as WSS remained significantly reduced. These hemodynamic and morphological observations are consistent with alterations in human patients. Using these coupled imaging and experimental results, we may determine changes in structure and function specific to CoA and correction and how they are influenced by hemodynamics and vascular biomechanics. We are now poised to augment clinical treatment of CoA through several methods, including investigation of specific cellular mechanisms causing morbidity in CoA and the development of therapies to improve endothelial function and restore vascular stiffness

Computational fluid dynamics indicators to improve cardiovascular pathologies

In recent years, the study of computational hemodynamics within anatomically complex vascular regions has generated great interest among clinicians. The progress in computational fluid dynamics, image processing and high-performance computing haveallowed us to identify the candidate vascular regions for the appearance of cardiovascular diseases and to predict how this disease may evolve. Medicine currently uses a paradigm called diagnosis. In this thesis we attempt to introduce into medicine the predictive paradigm that has been used in engineering for many years. The objective of this thesis is therefore to develop predictive models based on diagnostic indicators for cardiovascular pathologies. We try to predict the evolution of aortic abdominal aneurysm, aortic coarctation and coronary artery disease in a personalized way for each patient. To understand how the cardiovascular pathology will evolve and when it will become a health risk, it is necessary to develop new technologies by merging medical imaging and computational science. We propose diagnostic indicators that can improve the diagnosis and predict the evolution of the disease more efficiently than the methods used until now. In particular, a new methodology for computing diagnostic indicators based on computational hemodynamics and medical imaging is proposed. We have worked with data of anonymous patients to create real predictive technology that will allow us to continue advancing in personalized medicine and generate more sustainable health systems. However, our final aim is to achieve an impact at a clinical level. Several groups have tried to create predictive models for cardiovascular pathologies, but they have not yet begun to use them in clinical practice. Our objective is to go further and obtain predictive variables to be used practically in the clinical field. It is to be hoped that in the future extremely precise databases of all of our anatomy and physiology will be available to doctors. These data can be used for predictive models to improve diagnosis or to improve therapies or personalized treatments.En els últims anys, l'estudi de l'hemodinàmica computacional en regions vasculars anatòmicament complexes ha generat un gran interès entre els clínics. El progrés obtingut en la dinàmica de fluids computacional, en el processament d'imatges i en la computació d'alt rendiment ha permès identificar regions vasculars on poden aparèixer malalties cardiovasculars, així com predir-ne l'evolució. Actualment, la medicina utilitza un paradigma anomenat diagnòstic. En aquesta tesi s'intenta introduir en la medicina el paradigma predictiu utilitzat des de fa molts anys en l'enginyeria. Per tant, aquesta tesi té com a objectiu desenvolupar models predictius basats en indicadors de diagnòstic de patologies cardiovasculars. Tractem de predir l'evolució de l'aneurisma d'aorta abdominal, la coartació aòrtica i la malaltia coronària de forma personalitzada per a cada pacient. Per entendre com la patologia cardiovascular evolucionarà i quan suposarà un risc per a la salut, cal desenvolupar noves tecnologies mitjançant la combinació de les imatges mèdiques i la ciència computacional. Proposem uns indicadors que poden millorar el diagnòstic i predir l'evolució de la malaltia de manera més eficient que els mètodes utilitzats fins ara. En particular, es proposa una nova metodologia per al càlcul dels indicadors de diagnòstic basada en l'hemodinàmica computacional i les imatges mèdiques. Hem treballat amb dades de pacients anònims per crear una tecnologia predictiva real que ens permetrà seguir avançant en la medicina personalitzada i generar sistemes de salut més sostenibles. Però el nostre objectiu final és aconseguir un impacte en l¿àmbit clínic. Diversos grups han tractat de crear models predictius per a les patologies cardiovasculars, però encara no han començat a utilitzar-les en la pràctica clínica. El nostre objectiu és anar més enllà i obtenir variables predictives que es puguin utilitzar de forma pràctica en el camp clínic. Es pot preveure que en el futur tots els metges disposaran de bases de dades molt precises de tota la nostra anatomia i fisiologia. Aquestes dades es poden utilitzar en els models predictius per millorar el diagnòstic o per millorar teràpies o tractaments personalitzats.Postprint (published version

Novel Applications of Cardiovascular Magnetic Resonance Imaging-Based Computational Fluid Dynamics Modeling in Pediatric Cardiovascular and Congenital Heart Disease

Cardiovascular diseases (CVDs) afflict many people across the world; thus, understanding the pathophysiology of CVD and the biomechanical forces which influence CVD progression is important in the development of optimal strategies to care for these patients. Over the last two decades, cardiac magnetic resonance (CMR) imaging has offered increasingly important insights into CVD. Computational fluid dynamics (CFD) modeling, a method of simulating the characteristics of flowing fluids, can be applied to the study of CVD through the collaboration of engineers and clinicians. This chapter aims to explore the current state of the CMR-derived CFD, as this technique pertains to both acquired CVD (i.e., atherosclerosis) and congenital heart disease (CHD)

Echocardiography during submaximal isometric exercise in children with repaired coarctation of the aorta compared with controls

Objective Patients with repaired coarctation (RCoA) remain at higher risk of cardiac dysfunction, initially often only detected during exercise. In this study, haemodynamics of isometric handgrip (HG) and bicycle ergometry (BE) were compared in patients with RCoA and matched controls (MCs). Methods Case-control study of 19 children with RCoA (mean age 12.9 +/- 2.3 years; mean age of repair 7 months) compared with 20 MC. HG with echocardiography followed by BE was performed in both groups. Results During HG (blood pressure) BP increased from 114 +/- 11/64 +/- 4 mm Hg to 132 +/- 14/79 +/- 7 mm Hg, without significant differences. During HG as well as BE, HR increased less in patients with RCoA. There were no significant differences in (left ventricle) LV dimensions or LV mass. The RCoA group had diastolic dysfunction: both at rest and during HG they had significantly higher transmitral E and A velocities and lower tissue Doppler E' and A' velocities. E/E' was higher, reaching statistical significance during HG (p<0001). Conventional parameters of systolic function (FS and EF) were similar at rest and HG. More sensitive tissue Doppler S' was significantly lower at rest in CoA subjects (5.1 +/- 1.5 cm/s vs 6.5 +/- 1 +/- 1 cm/s; p<0.01), decreasing further during HG by 5% in the CoA group (NS) while unchanged in controls. Conclusions We provide first evidence that HG with echocardiography is feasible, easy and patient-friendly. A decreased systolic (tissue Doppler) and impaired diastolic LV function was measured in the RCoA group, a difference that tended to increase during HG

Incorporating the Aortic Valve into Computational Fluid Dynamics Models using Phase-Contrast MRI and Valve Tracking

The American Heart Association states about 2% of the general population have a bicuspid aortic valve (BAV). BAVs exist in 80% of patients with aortic coarctation (CoA) and likely influences flow patterns that contribute to long-term morbidity post-surgically. BAV patients tend to have larger ascending aortic diameters, increased risk of aneurysm formation, and require surgical intervention earlier than patients with a normal aortic valve. Magnetic resonance imaging (MRI) has been used clinically to assess aortic arch morphology and blood flow in these patients. These MRI data have been used in computational fluid dynamics (CFD) studies to investigate potential adverse hemodynamics in these patients, yet few studies have attempted to characterize the impact of the aortic valve on ascending aortic hemodynamics. To address this issue, this research sought to identify the impact of aortic valve morphology on hemodynamics in the ascending aorta and determine the location where the influence is negligible. Novel tools were developed to implement aortic valve morphology into CFD models and compensate for heart motion in MRI flow measurements acquired through the aortic valve. Hemodynamic metrics such as blood flow velocity, time-averaged wall shear stress (TAWSS), and turbulent kinetic energy (TKE) induced by the valve were compared to values obtained using the current plug inflow approach. The influence of heart motion on these metrics was also investigated, resulting in the underestimation of TAWSS and TKE when heart motion was neglected. CFD simulations of CoA patients exhibiting bicuspid and tricuspid aortic valves were performed in models including the aortic sinuses and patient-specific valves. Results indicated the aortic valve impacted hemodynamics primarily in the ascending aorta, with the BAV having the greatest influence along the outer right wall of the vessel. A marked increase in TKE is present in aortic valve simulations, particularly in BAV patients. These findings suggest that future CFD studies investigating altered hemodynamics in the ascending aorta should accurately replicate aortic valve morphology. Further, aortic valve disease impacts hemodynamics in the ascending aorta that may be a predictor of the development or progression of ascending aortic dilation and possible aneurysm formation in this region